Cardiovascular development in the zebrafish. II. Endocardial progenitors are sequestered within the heart field

Development ◽  
1994 ◽  
Vol 120 (12) ◽  
pp. 3361-3366 ◽  
Author(s):  
R.K. Lee ◽  
D.Y. Stainier ◽  
B.M. Weinstein ◽  
M.C. Fishman
Keyword(s):  
Cell Types ◽  
Spatial Gradient ◽  
Heart Cells ◽  
Cardiovascular Development ◽  
Heart Tube ◽  
Cardiac Progenitors ◽  
Distinct Cell ◽  
Heart Field ◽  
Relationship Of ◽  
Cardiac Patterning

We have examined the zebrafish embryo to ascertain the location of endocardial and myocardial progenitors prior to gastrulation, in an attempt to define the earliest stages of cardiac patterning. Currently there is uncertainty as to the spatial and lineage relationship of the progenitors for these two phenotypically distinct cell types that form the two concentric layers of the primitive heart tube. By single-cell injection and tracking, we distinguish a region in the early and midblastula which has the properties of a heart field, in that it defines a zone of cardiac progenitors within which there is a spatial gradient of propensity to generate heart cells, and which regulates, in the sense of adapting to the transplantation of pluripotential cells. This zone extends from the future ventral axis dorsally along the margin, with cardiogenic propensity tapering off laterally and dorsally. Myocardial progenitors are spread throughout this region, but endocardial precursors are restricted to the ventral marginal region. The cardiovascular progeny of the ventral cells include, in addition to endocardium and myocardium, cells in the endothelium and blood.

scholarly journals Outflow Tract Formation—Embryonic Origins of Conotruncal Congenital Heart Disease

2021 ◽  
Vol 8 (4) ◽  
pp. 42
Author(s):  
Sonia Stefanovic ◽  
Heather C. Etchevers ◽  
Stéphane Zaffran
Keyword(s):  
Congenital Heart ◽  
Cardiac Development ◽  
Heart Defects ◽  
Dynamic Structure ◽  
Cell Types ◽  
Outflow Tract ◽  
Heart Tube ◽  
Heart Field ◽  
Multiple Cell ◽  
The Many

Anomalies in the cardiac outflow tract (OFT) are among the most frequent congenital heart defects (CHDs). During embryogenesis, the cardiac OFT is a dynamic structure at the arterial pole of the heart. Heart tube elongation occurs by addition of cells from pharyngeal, splanchnic mesoderm to both ends. These progenitor cells, termed the second heart field (SHF), were first identified twenty years ago as essential to the growth of the forming heart tube and major contributors to the OFT. Perturbation of SHF development results in common forms of CHDs, including anomalies of the great arteries. OFT development also depends on paracrine interactions between multiple cell types, including myocardial, endocardial and neural crest lineages. In this publication, dedicated to Professor Andriana Gittenberger-De Groot and her contributions to the field of cardiac development and CHDs, we review some of her pioneering studies of OFT development with particular interest in the diverse origins of the many cell types that contribute to the OFT. We also discuss the clinical implications of selected key findings for our understanding of the etiology of CHDs and particularly OFT malformations.

scholarly journals Applications of miRNAs in cardiac development, disease progression and regeneration

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jeremy Kah Sheng Pang ◽  
Qian Hua Phua ◽  
Boon-Seng Soh
Keyword(s):  
Cardiac Development ◽  
Control Cell ◽  
Proliferative Potential ◽  
Heart Cells ◽  
Cardiovascular Development ◽  
Developmental Defects ◽  
Protein Coding ◽  
Cardiac Progenitors ◽  
Multiple Levels ◽  
Cell Niche

AbstractDevelopment of the complex human heart is tightly regulated at multiple levels, maintaining multipotency and proliferative state in the embryonic cardiovascular progenitors and thereafter suppressing progenitor characteristics to allow for terminal differentiation and maturation. Small regulatory microRNAs (miRNAs) are at the level of post-transcriptional gene suppressors, which enhance the degradation or decay of their target protein-coding mRNAs. These miRNAs are known to play roles in a large number of biological events, cardiovascular development being no exception. A number of critical cardiac-specific miRNAs have been identified, of which structural developmental defects have been linked to dysregulation of miRNAs in the proliferating cardiac stem cells. These miRNAs present in the stem cell niche are lost when the cardiac progenitors terminally differentiate, resulting in the postnatal mitotic arrest of the heart. Therapeutic applications of these miRNAs extend to the realm of heart failure, whereby the death of heart cells in the ageing heart cannot be replaced due to the arrest of cell division. By utilizing miRNA therapy to control cell cycling, the regenerative potential of matured myocardium can be restored. This review will address the various cardiac progenitor-related miRNAs that control the development and proliferative potential of the heart.

scholarly journals Hey2 restricts cardiac progenitor addition to the developing heart

2017 ◽  
Author(s):  
Natalie Gibb ◽  
Savo Lazic ◽  
Ashish R. Deshwar ◽  
Xuefei Yuan ◽  
Michael D. Wilson ◽  
...  
Keyword(s):  
Heart Development ◽  
Heart Defects ◽  
Myocardial Cell ◽  
Cell Number ◽  
Tube Formation ◽  
Heart Tube ◽  
Cardiac Progenitors ◽  
Developing Heart ◽  
Heart Field ◽  
A Cell

ABSTRACTA key event in vertebrate heart development is the timely addition of second heart field (SHF) progenitor cells to the poles of the heart tube. This accretion process must occur to the proper extent to prevent a spectrum of congenital heart defects (CHDs). However, the factors that regulate this critical process are poorly understood. Here we demonstrate that Hey2, a bHLH transcriptional repressor, restricts SHF progenitor accretion to the zebrafish heart. hey2 expression demarcated a distinct domain within the cardiac progenitor population. In the absence of Hey2 function an increase in myocardial cell number and SHF progenitors was observed. We found that Hey2 limited proliferation of SHF-derived cardiomyocytes in a cell-autonomous manner, prior to heart tube formation, and further restricted the developmental window over which SHF progenitors were deployed to the heart. Taken together, our data suggests a role for Hey2 in controlling the proliferative capacity and cardiac contribution of late-differentiating cardiac progenitors.

Abstract 16013: Direct Nkx2-5 Transcriptional Repression of Isl1 Controls Cardiomyocyte Subtype Identity

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Alexander Goedel ◽  
Tatjana Dorn ◽  
Jason T Lam ◽  
Franziska Herrmann ◽  
Jessica Haas ◽  
...  
Keyword(s):  
Heart Development ◽  
Transcriptional Repression ◽  
Embryonic Stem ◽  
Cardiac Differentiation ◽  
Heart Tube ◽  
Cardiac Progenitors ◽  
Gene Enhancer ◽  
Heart Field ◽  
Homeobox Protein ◽  
Islet 1

During heart development the second heart field (SHF) provides progenitor cells for most cardiomyocytes and expresses the LIM-homeodomain transcription factor Islet-1 (Isl1) and the homeobox protein Nkx2-5. Here, we show that a direct repression of Isl1 transcription by Nkx2-5 is necessary for proper specification and maturation of ventricular and atrial chamber-specific myocardial lineages. Overexpression of Nkx2-5 in mouse embryonic stem cells (ESCs) delayed specification of cardiac progenitors and inhibited expression of Isl1 and its downstream targets in the Isl1+ precursor population. These effects were partially rescued by Isl1 overexpression. Embryos deficient for Nkx2-5 in the Isl1+ lineage failed to downregulate Isl1 protein in cardiomyocytes of the heart tube (Figure 1A). We demonstrated that Nkx2-5 directly binds to an Isl1 gene enhancer and represses the transcriptional activity of Isl1. Furthermore, we showed that overexpression of Isl1 does not prevent cardiac differentiation of ESCs and in Xenopus laevis embryos. Instead, Isl1 overexpression in ESCs leads to enhanced specification of cardiac progenitors, earlier cardiac differentiation, and increased number of cardiomyocytes (Figure 1B). Functional and molecular analysis of Isl1-overexpressing cardiomyocytes revealed higher beating frequencies in both ESC-derived contracting areas and Xenopus Isl1-gain-of-function hearts (Figure 1C), which was associated with upregulation of nodal-specific genes and downregulation of transcripts of working myocardium. Our findings provide an Isl1/Nkx2-5-mediated mechanism that coordinately regulates the specification of cardiac progenitors towards the different myocardial lineages and ensures proper acquisition of myocyte subtype-identity (Figure 1D).

Pericardin, aDrosophilatype IV collagen-like protein is involved in the morphogenesis and maintenance of the heart epithelium during dorsal ectoderm closure

Development ◽  
2002 ◽  
Vol 129 (13) ◽  
pp. 3241-3253 ◽  
Author(s):  
Aymeric Chartier ◽  
Stéphane Zaffran ◽  
Martine Astier ◽  
Michel Sémériva ◽  
Danielle Gratecos
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Cell Types ◽  
Tube Formation ◽  
Extracellular Matrix Protein ◽  
Heart Cells ◽  
Dorsal Closure ◽  
Heart Tube ◽  
Pericardial Cells ◽  
Dorsal Ectoderm

The steps that lead to the formation of a single primitive heart tube are highly conserved in vertebrate and invertebrate embryos. Concerted migration of the two lateral cardiogenic regions of the mesoderm and endoderm (or ectoderm in invertebrates) is required for their fusion at the midline of the embryo. Morphogenetic signals are involved in this process and the extracellular matrix has been proposed to serve as a link between the two layers of cells.Pericardin (Prc), a novel Drosophila extracellular matrix protein is a good candidate to participate in heart tube formation. The protein has the hallmarks of a type IV collagen α-chain and is mainly expressed in the pericardial cells at the onset of dorsal closure. As dorsal closure progresses, Pericardin expression becomes concentrated at the basal surface of the cardioblasts and around the pericardial cells, in close proximity to the dorsal ectoderm. Pericardin is absent from the lumen of the dorsal vessel.Genetic evidence suggests that Prc promotes the proper migration and alignment of heart cells. Df(3)vin6 embryos, as well as embryos in which prc has been silenced via RNAi, exhibit similar and significant defects in the formation of the heart epithelium. In these embryos, the heart epithelium appears disorganized during its migration to the dorsal midline. By the end of embryonic development, cardial and pericardial cells are misaligned such that small clusters of both cell types appear in the heart; these clusters of cells are associated with holes in the walls of the heart. A prc transgene can partially rescue each of these phenotypes, suggesting that prc regulates these events. Our results support, for the first time, the function of a collagen-like protein in the coordinated migration of dorsal ectoderm and heart cells.

Transcriptional regulation of early cardiovascular development

2018 ◽  
Author(s):  
F. Gabriella Fulcoli ◽  
Antonio Baldini
Keyword(s):  
Transcription Factors ◽  
Current Knowledge ◽  
Cell Types ◽  
Regulatory Elements ◽  
Developmental Time ◽  
Special Focus ◽  
Cardiovascular Development ◽  
Cardiac Progenitors ◽  
Multiple Cell

The two major cardiac cell lineages of the vertebrate heart, the first and second cardiac fields (FHF and SHF), have different developmental ontogeny and thus different transcription programs. Most remarkably, the fate of cardiac progenitors (CPs) of the FHF is restricted to cardiomyocyte differentiation. In contrast, SHF CPs, which are specified independently, are maintained in a multipotent state for a relatively longer developmental time and can differentiate into multiple cell types. The identity of the transcription factors and regulatory elements involved in progenitor cell programming and fate are only now beginning to emerge. Apparent inconsistencies between studies based on tissue culture and in vivo embryonic studies confirm that the ontogeny of cardiac progenitors is strongly driven or affected by regionalization, and thus by the signals that they receive in different regions. This chapter summarizes current knowledge about transcription factors and mechanisms driving CP ontogeny, with special focus on SHF development.

Receptive fields and functional architecture of macaque V2

1994 ◽  
Vol 71 (6) ◽  
pp. 2517-2542 ◽  
Author(s):  
J. B. Levitt ◽  
D. C. Kiper ◽  
J. A. Movshon
Keyword(s):  
Receptive Fields ◽  
Cell Types ◽  
Macaque Monkey ◽  
Area V2 ◽  
Distinct Cell ◽  
Visual Areas ◽  
Layer 4 ◽  
Different Response ◽  
Relationship Of ◽  
The Relationship

1. Visual area V2 of macaque monkey cerebral cortex is the largest of the extrastriate visual areas, yet surprisingly little is known of its neuronal properties. We have made a quantitative analysis of V2 receptive field properties. Our set of measurements was chosen to distinguish neuronal responses reflecting parvocellular (P) or magnocellular (M) inputs and to permit comparison with similar measurements made in other visual areas; we further describe the relationship of those properties to the laminar and cytochrome oxidase (CO) architecture of V2. 2. We recorded the activity of single units representing the central 5 degrees in all laminae and CO divisions of V2 in anesthetized, paralyzed macaque monkeys. We studied responses to geometric targets and to drifting sinusoidal gratings that varied in orientation, spatial frequency, drift rate, contrast, and color. 3. The orientation selectivity and spatial and temporal tuning of V2 neurons differed little from those in V1. As in V1, spatial and temporal tuning in V2 appeared separable, and we identified a population of simple cells (more common within the central 3 degrees) similar to those found in V1. Contrast sensitivity of V2 neurons was greater on average than in V1, perhaps reflecting the summation of inputs in V2's larger receptive fields. Many V2 neurons exhibited some degree of chromatic opponency, responding to isoluminant color variations, but these neurons differed from V1 in the linearity with which they summate cone signals. 4. In agreement with others, we found that neurons with selective responses to color, size, and motion did seem to cluster in different CO compartments. However, this segregation of qualitatively different response selectivities was not absolute, and response properties also seemed to depend on laminar position within each compartment. As others also have noted, we found that CO stripe widths in the macaque (unlike in the squirrel monkey) did not consistently appear different. We relied on the segregation of qualitatively distinct cell types, and in some cases the pattern of Cat-301 staining as well, to distinguish CO stripes when the staining pattern of CO alone was ambiguous. Although all cell types were found in all CO compartments and laminae, unoriented cells were more prominent in layers 2–4 of “thin” stripes, direction-selective cells in layers 3B/4 of “thick” stripes, color-selective cells in the upper layers of thin and pale stripes, and end-stopped cells mainly outside of layer 4 in thin stripes.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiovascular development in the zebrafish. I. Myocardial fate map and heart tube formation

Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 31-40 ◽  
Author(s):  
D.Y. Stainier ◽  
R.K. Lee ◽  
M.C. Fishman
Keyword(s):  
Single Cell ◽  
Tube Formation ◽  
Cardiovascular Development ◽  
Heart Tube ◽  
Cell Stage ◽  
Animal Pole ◽  
Cardiac Progenitors ◽  
Somite Stage ◽  
The Future ◽  
Heart Tube Formation

We have analyzed the origin of cardiac progenitors in the zebrafish embryo by injection of single blastomeres with a lineage tracer dye, and examined the formation of the zebrafish heart tube by serial sectioning of immunostained embryos. At the 512-cell stage (early blastula), most cardiac progenitors lie in a marginal zone that extends from 90 degrees longitude (midway between the future dorsal and ventral axis) through 180 degrees longitude (the future ventral axis) to 270 degrees longitude. By focusing on myocardial progenitors located at 90 degrees (and 270 degrees) longitude, we found that a single cell injected in the early blastula can contribute progeny to both the atrium and ventricle. A cell injected in the midblastula contributes progeny to either the atrium or ventricle, but not both. This analysis suggests that, at least for these myocardial progenitors, the atrial and ventricular lineages separate in the midblastula. Precardiac cells involute early during gastrulation and turn towards the animal pole with other early involuting cells. These cardiogenic cells reach the embryonic axis around the 8-somite stage, and there they coalesce to form a pair of myocardial tubular primordia on either side of the midline. By the 21-somite stage, the tropomyosin-immunoreactive myocardial tubes have moved closer to each other, and a distinct group of cells, the endocardial progenitor cells, sits medially between them. The myocardial tubes then fuse to enclose the endocardial cells and form the definitive heart tube. By 22 hours postfertilization (26-somite stage), the heart tube is clearly beating. The regionalization of cardiac myosin heavy chain expression distinguishes the cardiac chambers at this stage, although they are not morphologically delineated until 36 hours. This work shows that cardiogenic regions can be identified in the early blastula, and that chamber restriction seems to arise in the midblastula. Additionally, it provides the basis for embryological perturbation at the single cell level, as well as for the genetic analysis of heart tube formation in the zebrafish.

scholarly journals The radial expression of dorsal-ventral patterning genes in placozoans, Trichoplax adhaerens, argues for an oral-aboral axis

2018 ◽  
Author(s):  
Timothy Q. DuBuc ◽  
Yuriy Bobkov ◽  
Joseph Ryan ◽  
Mark Q. Martindale
Keyword(s):  
Expression Patterns ◽  
Model Organism ◽  
Cell Types ◽  
Marine Animals ◽  
Axial Patterning ◽  
Trichoplax Adhaerens ◽  
Distinct Cell ◽  
Tgfb Signaling ◽  
Relationship Of ◽  
The Relationship

AbstractThe placozoans are a morphologically simplistic group of marine animals found globally in tropical and subtropical environments. They consist of a single named species, Trichoplax adhaerens and have roughly six morphologically distinct cell types. With a sequenced genome, a limited number of cell-types and a simple flattened morphology, Trichoplax is an ideal model organism to understand cellular dynamics and tissue patterning in the first animals. Using new approaches for identification of gene expression patterns this research looks at the relationship of Chordin/TgfB signaling and the axial patterning system of Placozoa. Our results suggest that placozoans have an oral-aboral axis similar to cnidarians and that the parahoxozoan ancestor (common ancestor of Placozoa and Cnidaria) was likely radially symmetric.

scholarly journals Understanding Mechanisms of Chamber-Specific Differentiation Through Combination of Lineage Tracing and Single Cell Transcriptomics

2021 ◽  
Author(s):  
David M Gonzalez ◽  
Nadine Schrode ◽  
Tasneem Ebrahim ◽  
Kristin G Beaumont ◽  
Robert Sebra ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Single Cell ◽  
Cardiac Development ◽  
Cell Types ◽  
Myocardial Cell ◽  
Lineage Tracing ◽  
Metabolic Processes ◽  
Heart Tube ◽  
Heart Field ◽  
Bona Fide

The specification and differentiation of atrial and ventricular myocardial cell types during development is incompletely understood. We have previously shown that Foxa2 expression during gastrulation identifies a population of ventricular fated progenitors, allowing for labeling of these cells prior to the morphogenetic events that lead to chamber formation and acquisition of bona fide atrial or ventricular identity. In this study, we performed single cell RNA sequencing of Foxa2Cre;mTmG embryos at the cardiac crescent (E8.25), primitive heart tube (E8.75) and heart tube (E9.25) stage in order to understand the transcriptional mechanisms underlying formation of atrial and ventricular cell types at the earliest stages of cardiac development. We find that progression towards differentiated myocardial cell types occurs primarily based on heart field progenitor identity, and that different progenitor populations contribute to ventricular or atrial identity through separate differentiation mechanisms. We identified a number of candidate markers that define such differentiation processes, as well as differential regulation of metabolic processes that distinguish atrial and ventricular fated cells at the earliest stages of development. We further show that exogenous injection with retinoic acid during formation of the cardiac primordia causes defects in ventricular chamber size and is associated with dysregulation in FGF signaling in anterior second heart field cells and a shunt in differentiation towards orthogonal lineages. Retinoic acid also causes defects in cell-cycle exit in myocardial committed progenitors that result in formation of hypomorphic ventricles with decreased expression of important metabolic processes and sarcomere assembly. Collectively, our data identify, at a single cell level, distinct lineage trajectories during cardiac progenitor cell specification and differentiation, and the precise effects of manipulating cardiac progenitor field patterning via exogenous retinoic acid signaling.

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